Apoptosis of endothelial cells is associated with paracrine induction of adhesion molecules: evidence for an interleukin-1beta-dependent paracrine loop.
Monocytic infiltration of the vessel wall is a hallmark of injury in a variety of vascular diseases. In the present study, we explored the relationship between endothelial apoptosis and hyperadhesiveness for monocytic cells. Apoptosis of human umbilical vein endothelial cells (HUVECs) was induced by either growth factor deprivation (GFD) for 24 hours or by incubation with mitomycin C (MMC) at 0.01 mg/ml for 24 hours and confirmed by light microscopy and DNA laddering. In parallel assessments of cell-cell adhesion, GFD and MMC induced hyperadhesiveness of HUVECs for the THP-1 monocytic cell line. Hyperadhesiveness developed in association with induction of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 on HUVECs and was attenuated by monoclonal antibodies directed against these ligands. Culture medium conditioned by apoptotic HUVECs up-regulated the expression of adhesion molecules on normal HUVECs, suggesting that paracrine factors in the apoptotic milieu led to induction of adhesion molecules. Interleukin (IL)-1beta was implicated as a putative mediator in this setting because 1) exogenous IL-1beta up-regulates ICAM-1 and VCAM-1 with kinetics similar to those noted during endothelial cell apoptosis, 2) endothelial apoptosis was associated with increased expression of IL-1beta converting enzyme, and 3) the adhesion-promoting actions of GFD and MMC were attenuated by an anti-IL-1beta antibody.
Hébert
M J
MJ
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Gullans
S R
SR
Mackenzie
H S
HS
Brady
H R
HR
D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D015815:Cell Adhesion Molecules; D006728:Hormones; D007375:Interleukin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1